TRIM24 is an oncogenic transcriptional co-activator of STAT3 in glioblastoma

• DOI: 10.1038/s41467-017-01731-w
• Publication Date: 2017-11-07T14:42:37Z
• Authors: Deguan Lv; Yanxin Li; Weiwei Zhang; Angel A. Alvarez; Lina Song; Jianming Tang; Wei-Qiang Gao; Bo Hu; Shi-Yuan Cheng; Haizhong Feng
• Keywords: Chromatin immunoprecipitation

Abstract Aberrant amplification and mutations of epidermal growth factor receptor (EGFR) are the most common oncogenic events in glioblastoma (GBM), but mechanisms by which they promote aggressive pathogenesis not well understood. Here, we determine that non-canonical histone signature acetylated H3 lysine 23 (H3K23ac)-binding protein tripartite motif-containing 24 (TRIM24) is upregulated clinical GBM specimens required for EGFR-driven tumorigenesis. In multiple glioma cell lines patient-derived stem cells (GSCs), EGFR signaling promotes H3K23 acetylation association with TRIM24. Consequently, TRIM24 functions as a transcriptional co-activator recruits STAT3, leading to stabilized STAT3-chromatin interactions subsequent activation STAT3 downstream signaling, thereby enhancing Our findings uncover pathway signal relay suggest potential therapeutic target associated activation.